Q. This is regarding examination of externally normally formed fetuses in surgical pathology: Below what weight or gestational age is it acceptable practice to omit inspection of the internal organs and sampling of internal organs for histology?

A. This is a mixture of local government regulations and surgical pathology policy. The first issue is whether the fetus counts as a fetal death—that is, at or above 20 weeks in Connecticut; perhaps different rules apply in other states. If so, the remains should be treated like any other patient death: They should go to the morgue, and, if there is an autopsy permit, they should be examined as the remains are examined in any other autopsy. The placenta should go to surgical pathology for a standard examination, though, in the event the fetus is autopsied, some institutions may prefer to examine the placenta as part of the autopsy examination. At the very least, the autopsy report should refer to the surgical pathology report of the placental findings.

For fetuses less than 20 weeks, our first decision point at Yale-New Haven Hospital is whether the clinicians/parent(s) have requested an autopsy. If there is a signed autopsy permit, the fetus (with or without placenta, as above) goes to the autopsy suite and a full, standard autopsy is performed. No surgical pathology exam is done. If there is no autopsy permit and the fetus is less than 20 weeks gestational age, the fetus is treated as a surgical specimen.

This is where surgical pathology policy kicks in. The placenta for any spontaneous intrauterine demise should always be examined, grossly and histologically. I also recommend that the fetus be routinely examined internally and histologically, regardless of gestational age, weight, or both. Internal gross examination can reveal findings that are not apparent externally (situs inversus, asplenia, malrotation of the gut, for example), and some of these may have implications for subsequent pregnancies.

As for the histologic examination, in almost no cases is this likely to reveal anything. The main benefit here, however, is that you are archiving genetic material. Any tissue not submitted for histology will most likely be incinerated within a few weeks. Submitting tissue on the fetus ensures DNA from that fetus will be available for at least 10 years (current mandated retention time for surgical pathology blocks), and this may become relevant if subsequent issues of genetic diseases, parentage, polymorphisms, etc., arise. Yes, the placenta will also be predominantly fetal tissue as well, but there is likely to be maternal tissue/blood admixed, which may complicate increasingly sensitive genetic analyses.

Q. How should one deal with a hemolyzed or icteric specimen for a CBC?

A. Specimens with increased bilirubin (icteric specimens) do not generally interfere with the performance of a CBC. Elevated bilirubin levels may be associated with hemolysis, which does affect the CBC.

Hemolysis, if significant, is always a problem primarily because of the plasma hemoglobin and, depending on the mechanism of the hemolysis, secondarily because of effects on cellular elements. Whenever there is significant hemolysis there will be a discrepancy between the hemoglobin (measured after lysis of red cells so it includes both cellular and plasma hemoglobin) and red cells/hematocrit (based only on intact cells). If the hemolysis is a result of improper specimen collection, it is a cause for specimen rejection and re-collection. If the hemolysis truly represents the condition of the patient (intravascular red cell destruction), then the discrepancy is expected and the laboratory should note it and indicate its cause. In centers that perform plasma hemoglobin determinations, it would be possible to correct the hemoglobin value by measuring and subtracting the plasma hemoglobin and substituting that hemoglobin value in the CBC, which should match the red cells/ hematocrit and allow for calculating correct indices. The problem of the plasma hemoglobin could also be avoided with plasma substitution techniques. In practice, these corrections are rarely done.

Certain causes of hemolysis can cause problems with other CBC parameters. Strong cold agglutinins, in addition to causing hemolysis, cause cell clumping that leads to undercounting of red cells and false increases in the MCV and MCH. The clumping can be avoided, to some extent, by keeping the specimen warm (body temperature) until analysis. An anemia that causes red cell fragmentation, especially one that results in a number of small fragments, can lead to a spuriously low red count and elevated platelet count due to miscounting the red cell fragments as platelets. In such a case, review of the blood smear is essential to recognize the problem and perform a platelet estimate from the smear, which will more accurately reflect the platelet number. In centers that have patients with problems that invariably lead to intravascular hemolysis (for example, patients on ECMO or with severe burns), a system should be in place to recognize the hemolysis, review clinical diagnosis and previous results and a blood smear, and based on these findings, provide the most appropriate and accurate results possible.